Which precautions should be taken when using NGS to investigate the cause of a genetic disease?

When using NGS to investigate the cause of a disease, clinicians and patients must be aware that the test may cover many genes, most of them unrelated to the patient’s disease. This would lead to discovery of secondary or incidental findings on genes causing other diseases, e.g. cancer predisposition status (Kuhlen and Borkhardt 2015). Recently, policy statements from two major regulatory agencies (AMP and ACMG) have provided a list of recommendations (Green et al. 2013; Allyse and Michie 2013; ACMG Board of Directors 2015; Hegde et al. 2015). However, each country has its own directives about incidental finding reporting. Therefore, it is extremely important that the patient, or their legal representative, is informed of the incurred risks and patient decision is recorded in an “informed consent” document (Anderson et al. 2016). It is the responsibility of the treating clinician to collect the informed consent form before ordering any NGS test, and ensure that patient understands the potential outcomes of the test.